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pmid:35065633
High expression of PDZ-binding kinase is correlated with poor prognosis and immune infiltrates in hepatocellular carcinoma.
Wei Mu · Yaoli Xie · Jinhu Li · Runzhi Yan · Jingxian Zhang · Yu'e Liu · Yimin Fan
World journal of surgical oncology · 2022 doi:10.1186/s12957-021-02479-w
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Complete file
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There is evidence that overexpression of this gene is associated with tumorigenesis. However, the role of PBK in hepatocellular carcinoma (HCC) remains unclear. Therefore, we evaluated the prognostic role of PBK and its correlation with immune infiltrates in hepatocellular carcinoma.\nMETHODS: The expression of PBK in pan-cancers was studied by Onconmine and TIMER. The expression of PBK in HCC patients and its relationship with clinicopathological characteristics were analyzed using The Gene Expression Profiling Interactive Analysis (GEPIA), The human protein atlas database (HPA), The Cancer Genome Atlas (TCGA), and Gene Expression Omnibus (GEO) databases. Receiver operating characteristic (ROC) curve was used to determine the diagnostic value of PBK in HCC patients. The relationship between PBK and prognosis of HCC was performed by GEPIA and Kaplan Meier plotter web tool. The correlations between the clinical characteristics and overall survival were analyzed by Univariate Cox regression and Multivariate Cox hazards regression to identify possible prognostic factors for HCC patients. LinkedOmics was applied to investigate co-expression associated with PBK and to analyze Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The network map of PBK and related genes is constructed by GeneMANIA. Finally, TIMER and TISIDB were used to analyze the correlations between PBK and tumor-infiltrating immune cells.\nRESULTS: Multiple database analysis shows that PBK was highly expressed in many types of tumors, including hepatocellular carcinoma, and was significantly related to tumor stage (P=0.0089), age (P=0.0131), and race (P=0.0024) of HCC patients. The receiver operating characteristic (ROC) curve analysis showed that PBK had high diagnostic potential to HCC in GSE76427 (AUC=0.8799), GSE121248 (AUC=0.9224), GSE62232 (AUC=0.9975), and GSE84402 (AUC=0.9541). Multivariate Cox hazards regression showed that high expression of PBK may be an independent risk factor for overall survival in HCC patients (HR = 1.566, 95% CI=1.062-2.311, P= 0.024). The Protein-protein interaction network showed that PBK significantly interacted with LRRC47, ARAF, LGALS9B, TTK, DLG1, and other essential genes. Furthermore, enrichment analysis showed that PBK and co-expressed genes participated in many biological processes, cell composition, molecular functions, and pathways in HCC. Finally, the immune infiltration analysis by TIMER and TISIDB indicated that a significant tightly correlation between PBK and macrophages, neutrophils, as well as chemokines and receptors.\nCONCLUSIONS: High expression of PBK is significantly correlated with poor survival and immune infiltrates in hepatocellular carcinoma. Our study suggests that PBK can be used as a biomarker of poor prognosis and potential immune therapy target in hepatocellular carcinoma.", "claims": [{"id": "claim-method", "statement": "The correlations between the clinical characteristics and overall survival were analyzed by Univariate Cox regression and Multivariate Cox hazards regression to identify possible prognostic factors for HCC patients.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35065633", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "The correlations between the clinical characteristics and overall survival were analyzed by Univariate Cox regression and Multivariate Cox hazards regression to identify possible prognostic factors for HCC patients."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data used to support the findings of this study are included in the article.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35065633", "locator": "sections[28] \"notes\" paragraph 1", "quote": "The data used to support the findings of this study are included in the article."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Multivariate Cox hazards regression showed that high expression of PBK may be an independent risk factor for overall survival in HCC patients (HR = 1.566, 95% CI=1.062–2.311, P= 0.024).", "kind": "quantitative", "target": {"value": 95.0, "unit": "per cent", "tolerance": null, "source": "Multivariate Cox hazards regression showed that high expression of PBK may be an independent risk factor for overall survival in HCC patients (HR = 1.566, 95% CI=1.062–2.311, P= 0.024)."}, "evidence": [{"asset": "source:pmid:35065633", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Multivariate Cox hazards regression showed that high expression of PBK may be an independent risk factor for overall survival in HCC patients (HR = 1.566, 95% CI=1.062–2.311, P= 0.024)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Multivariate Cox hazards regression showed that high expression of PBK may be an independent risk factor for overall survival in HCC patients (HR = 1.566, 95% CI=1.062–2.311, P= 0.024).", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:35065633"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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